[Aim] We analyzed the secretion ability of cytokines from peripheral blood mononuclear cells (PBMC) and the number of peripheral blood Tregs before and after adoptive T cell therapy (CD3-LAK) in order to assess the relation of the immunological responses and the efficacy of the treatment.

[Method] Patients who received CD3-LAK treatment more than four times were done an entry of this study. We conducted this study after having obtained the informed consent of the study for these patients. We measured the secretion ability of cytokines from PBMC using the peripheral blood collected from the patients before treatment and 2 weeks later after the 4th treatment. The methods we measured the secretion ability of cytokines are shown below. IFN-alpha: We stimulated the whole blood by Sendai virus for 20 hours, and IFN-alpha of supernatant was measured by bioassay. The other cytokines (IL-2, IL-4, IL-10, TNF-alpha, IFN-gamma etc): We stimulated the whole blood by PHA for 48 hours, and the cytokines of supernatant were measured by BioPlex array. In terms of the change of the number of peripheral blood Tregs, we analyzed Foxp3 and CD4 positive T cells by flow cytometry.

[Result] The values of IFN-gamma and TNF-alpha were significantly high after the treatment. Ratio of Treg to CD4 was significantly low after the treatment. The survival time of the group of patients in whom the number of Treg decreased after the treatment was longer than that of the other group of patients.

[Discussion] We found that even in patients with refractory advanced cancer, the therapeutic intervention of CD3-LAK makes positive change - the secretion ability of cytokines from PBMC shifts to Th1, the number of Treg in peripheral blood decreases. And it suggests that adoptive T cell therapy influences immunoescape mechanism in patients with cancer. It will be necessary to clarify the mechanism of the effect and to develop an adoptive immunotherapy which has more beneficial clinical effect.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1933.